Efficacy, Tolerability and Safety of Early Introduction of Everolimus, Reduced Calcineurin Inhibitors and Early Steroid Elimination Compared to Standard CNI, Mycophenolate Mofetil and Steroid Regimen in Paediatric Renal Transplant Recipients
The purpose of this study is to determine if everolimus combined with reduced exposure CNI (TAC) is efficacious and safe and will support corticosteroid elimination compared to a standard exposure CNI (TAC) + MMF + steroid regimen after paediatric kidney transplantation. An additional purpose of the study is to assess the effect of the combination of EVR and reduced exposure CNI (TAC) on renal function.
This study is part of the requirements of the Paediatric Investigational Plan approved by Paediatric Committee at the European Medicines Agency (PDCO/EMA) on September 10, 2010, and is intended to support the indication of everolimus in the prevention of acute rejection in paediatric recipients of a renal transplant.
Prevention of Acute Rejection in Paediatric Recipients of a Renal Transplant
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
- Composite efficacy endpoint of biopsy-proven acute rejection [ Time Frame: 12 months post transplantation ] [ Designated as safety issue: Yes ]To estimate the rate of the composite efficacy endpoint of biopsy-proven acute rejection (BPAR), graft loss or death at 12 months post transplantation in primary paediatric kidney transplant recipients converted at 4-6 weeks post-transplantation from MMF + standard TAC regimen and steroids, to everolimus + reduced dose TAC regimen and steroid withdrawal at 6 months, versus continuation of MMF + standard TAC regimen and steroids.
- Renal function. [ Time Frame: 12 months post-transplantation ] [ Designated as safety issue: Yes ]To evaluate renal function assessed by Glomerular Filtration Rate (eGFR) estimated by the Schwartz Formula (abbreviated and extended) (Schwartz, 2009).
- Composite efficacy endpoint [ Time Frame: at 12 and 36 months post-transplantation ] [ Designated as safety issue: No ]To evaluate the proportion of patients with the following efficacy events: Biopsy Proven Acute Rejection (BPAR), graft loss or death. The efficacy events will be descriptively summarized by treatment group.
- Incidence of biopsy proven antibody mediated rejection. [ Time Frame: at 12 and 36 months post-transplantation ] [ Designated as safety issue: No ]To evaluate the proportion of patients with the following efficacy events: biopsy proven antibody mediated rejection/Steroid resistant BPAR and BPAR treated with T cell depleting therapy.
- Chronic allograft nephropathy [ Time Frame: at 12 and 36 months post-transplantation. ] [ Designated as safety issue: No ]To evaluate the proportion of patients with chronic allograft nephropathy (interstitial fibrosis and tubular atrophy, IF/TA) by histopathology and its progression.
- Proteinuria (urinary protein/creatinine ratio) [ Time Frame: at 12 and 36 months post-transplantation ] [ Designated as safety issue: No ]The urinary protein/creatinine ratio will be descriptively summarized by treatment group at each visit. The incidence rate of patients with proteinuria will be categorized in <0.2 mg/mg, 0.2<2.0 mg/mg and ≥ 2.0 mg/mg and summarized by treatment groups at each visit.
- Growth/development [ Time Frame: at 12 and 36 months post-transplantation. ] [ Designated as safety issue: No ]evaluation of the potential effects upon the gonadal axis and bone growth.
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||May 2017|
|Estimated Primary Completion Date:||May 2017 (Final data collection date for primary outcome measure)|
Experimental: Investigational arm
Conversion from MMF to everolimus plus reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
Everolimus (C0 trough level of 3-8 ng/mL) in combination with reduced dose tacrolimus and steroids withdrawal at 6 months after transplant
Active Comparator: Control arm
MMF continuation (in combination with tacrolimus and standard dose steroids)
MMF (Cellcept®): 600mg/m2/dose twice daily (1200 mg/m2/day) in combination with tacrolimus (Prograf) and standard dose steroids
|Contact: Novartis Pharmaceuticals||1-888-669-6682|
|Contact: Novartis Pharmaceuticals|
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|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|